We propose to study the system responsible for growth regulation in mammalian cells by using the estrogen-receptor protein of uterus as a probe. Upon binding 17 Beta-estradiol, this protein is known to migrate from the cell cytoplasm to the nucleus. Thereafter, those cells which contain the receptor begin to grow rapidly. In the uterine nucleus the receptor appears to be bound to chromatin; in vitro, we find that the purified receptor binds tightly to DNA. Beginning with DNA-cellulose chromatography, we are purifying the receptor to homogeneity. Sensitive binding assays will then be used to test solubilized chromatin proteins for proposed regulatory species which interact with the receptor, and to isolate special restriction nuclease pieces of eukaryotic DNA which bind receptor tightly. In parallel with these studies, cell-lines which respond to estrogens in tissue culture will be sought. Such cell-lines will facilitate tracing the path of the receptor through the nucleus. In addition, they should make possible isolation of mutant cells which no longer respond to estradiol because of altered regulatory components.